It is proposed to devise methods for establishing the stereochemical courses of enzymatic reactions involving bond cleavage at phosphorous and to apply them to stereochemical studies on nucleotidyltransferases and phosphotransferases, including terminal deoxynucleotidyl transferase, and acyl t-RNA synthetase, adenyl cyclase, CAMP phosphodiesterase, nucleoside monophosphotransferase, and DNA polymerases. The methods to be developed and applied will involve the use of sulfur analogs of nucleotides labeled with 180 as alternative substrate for these enzymes and mass spectral and NMR analysis of products.